Angiogenesis, the process of developing a hemovascular network from pre-existing blood vessels, is essential for the growth of solid tumors and is a component of normal wound healing and growth processes. It also has been implicated in the pathophysiology of many diseases and conditions, including atherogenesis, arthritis, psoriasis, corneal neovascularization, and diabetic retinopathy.
The molecular messengers responsible for the process of angiogenesis have long been sought. For example, a variety of soluble mediators have been implicated in the induction of neovascularization. These include prostaglandins (Auerbach, in Lymphokines, Pick and Landy, eds., 69-88, Academic Press, New York, 1981), human urokinase (Berman et al., Invest. Opthalm. Vis. Sci. 22: 191-199, 1982), copper (Raju et al., J. Natl. Cancer Inst. 69: 1183-1188, 1982), and various “angiogenesis factors” (for instance, see U.S. Pat. No. 4,916,073). The most often cited angiogenic growth factors are basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF).
Because angiogenesis factors play an important role in wound healing (Rettura et al., FASEB Abstract #4309, 61st Annual Meeting, Chicago, 1977) and the development of malignancies (Klagsburn et al., Cancer Res. 36: 110-114, 1976; and Brem et al., Science 195: 880-881, 1977), it would be advantageous to identify new angiogenic and anti-angiogenic agents.